Design, synthesis of novel pyranotriazolopyrimidines and evaluation of their anti-soybean lipoxygenase, anti-xanthine oxidase, and cytotoxic activities. (1st November 2016)

• Record Type: Journal Article
• Authors: Saïd, Abderrahim Ben; Romdhane, Anis; Elie, Nicolas; Touboul, David; Jannet, Hichem Ben; Bouajila, Jalloul
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 6(2016:Dec.)
• Page Start: 1277
• Page End: 1285
• Publication Date: 2016-11-01
• Subjects: Amidoximes -- cytotoxic activity -- soybean lipoxygenase inhibition -- triazolo[1, 5-c]pyrimidine, 1, 2, 4-oxadiazole -- xanthine oxidase inhibition; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2015.1118684
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: The synthesis of 14-(aryl)-14 H -naphto[2, 1- b ]pyrano[3, 2- e ][1, 2, 4]triazolo[1, 5- c ]pyrimidine-2-yl) acetamidoximes2a –e has been accomplished by reaction of 2-acetonitrile derivatives1a –e with hydroxylamine. Cyclocondensation reaction of precursors2a –e with some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives3a –e, 4a –e, and5a –e, respectively. On the other hand, the reaction of precursors2a –e with 2-chloropropanoyl chloride afforded the new acetimidamides6a –e which evolve under reflux of toluene to the new oxadiazoles7a –e . The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i)5a was the most active (IC50 = 4.0 μM) and selective against MCF-7 and (ii)2a was cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 μM, respectively) while2e is highly selective against OVCAR-3 (IC50 = 10 μM).